17beta-Methoxy-5alpha-androstan-3-one → 3beta-Methyl-3alpha-hydroxy-17beta-methoxy-5alpha-androstane
Reaction equation
[CH3:1][O:2][C@H:3]1[CH2:8][CH2:7][C@H:6]2[C@H:9]3[C@H:19]([CH2:20][CH2:21][C@:4]12[CH3:5])[C@:17]1([CH3:18])[C@H:12]([CH2:13][C:14](=[O:22])[CH2:15][CH2:16]1)[CH2:11][CH2:10]3.[Li][CH3:24]>C1COCC1.C(Cl)Cl>[CH3:24][C@@:14]1([OH:22])[CH2:15][CH2:16][C@@:17]2([CH3:18])[C@@H:12]([CH2:11][CH2:10][C@@H:9]3[C@@H:19]2[CH2:20][CH2:21][C@@:4]2([CH3:5])[C@H:6]3[CH2:7][CH2:8][C@@H:3]2[O:2][CH3:1])[CH2:13]1Participants
Conditions
- Temperature
- -78 °C
Procedure
A solution of 17β-methoxy-5α-androstan-3-one (101 mg, 0.33 mmol) in dry THF (20 mL) was treated with MeLi (1 mL, 1.5M in THF, 1.5 mmol) at −75° C. After stirring the mixture at −78° C. for 0.5 hr, the mixture was quenched with NH4Cl solution (5 mL). The solvents were removed and the residue was extracted with EtOAc. The organic layer was washed with water, and brine. After drying over anhyd. MgSO4 the solution was filtered and evaporated to yield the crude product. This crude product was then dissolved in a small amount of CH2Cl2 and poured on a column of silica gel. Elution with toluene:acetone mixture (95:5) gave 3β-methyl-3α-hydroxy-17β-methoxy-5α-androstane (35 mg); mp 151-154° C.; TLC Ff (hexane:acetone 7:3)=0.43; and then 3α-methyl-3β-hydroxy-17β-methoxy-5α-androstane (30 mg) as a colorless solid; TLC Rf (hexane:acetone 7:3)=0.27.
Workup
- customthe mixture was quenched with NH4Cl solution (5 mL)
- customThe solvents were removed
- extractionthe residue was extracted with EtOAc
- washThe organic layer was washed with water, and brine
- customAfter drying over anhyd
- filtrationMgSO4 the solution was filtered
- customevaporated
- customto yield the crude product
- additionpoured on a column of silica gel
- washElution with toluene
Sources & evidence
- ORD record
- ord-d6bfb580fbdf45a6b6b4359c17b03e5d
- Source dataset
- uspto-grants-2004_08
- Patent number
- US06780853B1
Reaction notes
Loading…